Pancreatic islet transplantation has the potential to be the most physiologically advantageous and minimally invasive procedure for treatment of type I diabetes mellitus. However, despite progressively increasing numbers of islet transplants in these patients, the endocrine function established by the transplant is far from optimum. In order for this approach to be a clinically acceptable diabetes therapy, several technical and immunological problems need to be solved.
Donor islet preparation is the first critical step to provide a sufficient number of high quality islets for transplantation. Large-scale islet preparation from the pancreas of large animal species, including dogs, pigs and humans, has become possible through the development of highly automated procedures. Islet isolation, involving the digestion of pancreatic tissue and the purification of islets, is, in particular, the most important process that influences the outcome of transplants.
Pancreatic islets are usually transplanted into diabetic patients who also need a kidney or other solid organ transplant who are already being, or will be treated with immunosuppressants in order to prevent graft rejection. Despite many attempts, to date only a small fraction of islet allografts have functioned for a prolonged period. One of the major reasons for this failure appears to be an insufficient number of islets used for transplantation. The current recommendation by the International Islet Transplant Registry is to transplant more than 6,000 islets, equivalent to 150 .mu.m in size, per kg of the recipient's body weight in order to achieve long-term maintenance of euglycemia. To fulfill this requirement, islets from multiple donors have often been used. However, a more desirable approach would be to derive both kidney (or other organs) and islets from the same donor in order to avoid an additional antigenic load and therefore, decrease the possibility of rejection. This would require the isolation of a large number of high quality islets from a single human pancreas.
Large-scale islet isolation from the human pancreas has become possible with advances in technology and the availability of high quality collagenase used in their preparation. However, even with these improvements, the islet yield from a single pancreas is often insufficient for transplantation. It is desirable to develop a method for isolation of pancreatic islets and storage of the islets so that transplants can be prepared from a single donor.